PROJECTSUMMARY/ABSTRACT ThisisaproposaltoacquireaThermoQExactiveHFmassspectrometerandaconventionalflowUPLCfora rangeofmetabolomicsassaysincludinguntargeted(global)metabolitecomparisons,fluxanalyses,and lipidomicsprofiling(untargetedandtargeted).Thisinstrumentisneededtosupport8majorusersand2other usersattheWistarInstitutetoconductmetabolismandlipidomestudiesinvolving22NIHgrants.Eightof theseusershavemultipleNIHgrantsthatwillbenefitfromtherequestedmassspectrometersystem.Oneof theotherusersisDr.ZacharySchugwhodoesnotyethaveNIHfundingbecauseherecentlymovedfromhis postdoctoralpositioninScotlandtotheWistarInstitute.Dr.Schugisacriticalcontributortothisproposal becausehehasin-depthexpertiseinalloftheanalyticalapproachesthatwillbeused.Itisestimatedthatthis usergroupwillinitiallyrequirenearlyallavailabletimeontherequestedinstrument.However,weexpectto improvethroughputwithexperienceandanticipatethatinfutureyearsthenumberofuserswillgrow substantially,therebyensuringthatthisinstrumentwillcontinuetobeheavilyutilized.Acquisitionofthis instrumentandexpansionofourmetabolomicscapacityispartofastronginstitutionalcommitmentdrivenby theexpandingroleofmetabolisminmultipleaspectsofcancerbiologyandotherhumandiseases,coupled withverylimitedandinadequateaccesstothesetechnologiesfromexternalsources.Asaresult,metabolism studiesattheWistarInstitutehavesometimesnotbeenpursuedduetologisticalbarriersandstudiesthatwere pursuedsometimessufferedfromthelackofadequateconsultativeexpertisetoensureoptimalexperiment design.TherequestedsystemwillbehousedintheWistarInstituteProteomicsandMetabolomicsCore FacilityunderthesupervisionoftheFacility?sScientificDirector,Dr.DavidSpeicher.Day-to-daymaintenance andoperationoftheinstrumentwillbehandledbyDr.HamidBaniasadi,whotrainedinDanRaftery?slaband hasmorethan8yearsofexperiencewithdevelopingandusingmetabolomicsassays.Inaddition,Dr.Zachary Schug,whoisarecentlyrecruitedassistantprofessorfromEyalGottlieb?slab,willprovideexpertconsultative adviceandwilltrainandeducateusersthroughtrainingworkshops,ametabolomicsjournalclub,and individualconsultationasneeded.TheWistarInstitute?sCEOandCancerCenterDirectorconfirmsthe Institute?sverystrongcommitmenttoimplementingandmaintainingstate-of-the-artmetabolomicscapacities. Wistarhasalreadyinvestedmorethan$1.6Minmetabolomicsexpertiseandcapacities.Specifictothisgrant, theInstituteiscommittedto:1)providingthe$66,571balanceofthepurchasepriceabovetheSIGcap,2) coveringanycostsassociatedwithinstrumentinstallation,3)ensuringsupportisavailableforexpertoperators andinstrumentmaintenancethroughoutitsusefullifetime,and4)ensuringthatNIHfundedinvestigatorshave primaryaccesstotheinstrument.